Composition of medicine for treating headache disease and process of preparation and uses thereof

ABSTRACT

This invention relates to a medicine combination used to treat headache, which is made up of Chuanxiong and Tianma in a certain scientific weight proportion. The medicine combination can be made into any commonly used dosage form. The invention also provides other applications of this medicine combination in the production of an anti-oxidative drug, an antihypertensive drug, a platelet antiaggregation drug, an antithrombosis drug and an anticoagulant.

FIELD OF THE INVENTION

This invention is related to a kind of combination of medicines to treatheadache, especially a combination of medicines which are made from theChinese herbal medicine that can cure headache. This invention is alsorelated to the preparation of this medicine combination and applicationsin the pharmaceutical field—the traditional Chinese medicine field.

BACKGROUND OF THE INVENTION

Headache, especially the vascular headache, is a commonly encountereddisease and frequently occurring disease. Vascular headache includes thetype of vascular hemicrania and the type of vascular nonhemicrania.Based on the domestic and international statistical data, the incidencerate of vascular headache is about 4-6%, while the incidence rate inChina is about 6.3%. Estimated on this data, the number of the patientssuffering from the vascular headache in China is about6,000,000-8,000,000, while the actual number may be even more. Thisdisease seriously affects people's usual work, study, health and life.

In the recent decades, more and more attention was paid to this diseasein the modern medicine. The majority of the scholars believe that themechanism of vascular headache is related to the genetic factors, thedysfunction of the cerebrovascular relaxation-contraction movement, thevitium of the blood brain barrier, the dysfunction of the internalsecretion, the concentration change of the bradykinin, 5-HT, histamineand the other vaso-active substances, the enhancement of the plateletaggregative function and adhesive function. By now, the main therapiesof the vascular headache include: vasoconstrictor, antiserotonin,inhibitor of the platelet aggregation, antihistamine, β-receptorblocking agent, tranquilizer, several kinds of hormone, oxygen therapyin the high pressure situation and the surgical therapies such as thecutting off the sympathetic nerve and the ligation of the specialvessels out of skull. But the effects are not very ideal, especially theeffects in the future. Additionally, all these therapies have many sideeffects.

SUMMARY OF THE INVENTION

By taking advantage of the plentifulness of the Chinese herbal medicinein combination with the modem pharmacological, toxicological andclinical research findings of the Chinese herb medicine, we selected twoherbs: Chuanxiongiong (Rhizome of chuanxiong)—with the function ofactivating blood circulation to dissipate blood stasis, and Tianma(Rhizome of tall gastrodia)—with the function of calming the wind andrelieving convulsion and spasm, then searched out a scientific way ofcompatibility and an elaborate preparation method. On these bases wemade out this invention's technical proposal.

The first purpose of this invention is to provide a medicinecombination, which has a remarkable function of anticoagulant,antianoxic, depressurizing, calming and antalgic, to treat headache.

The second purpose of this invention is to provide the specialpreparation of this medicine combination.

The third purpose of this invention is to provide the application ofthis medicine combination in the manufacture of other medicines used totreat headache. These medicines include the drug to treat the vascularheadache and the drug to treat the neural headache.

The fourth purpose of this invention is to provide the application ofthis medicine combination in the manufacture of the antianoxic drug.

The fifth purpose of this invention is to provide the application ofthis medicine combination in the manufacture of antihypertensive drug.

The sixth purpose of this invention is to provide the application ofthis medicine combination in the manufacture of the plateletanticoagulant.

The seventh purpose of this invention is to provide the application ofthis medicine combination in the manufacture of the anti-thrombosisdrug.

The eighth purpose of this invention is to provide the application ofthis medicine combination in the manufacture of the anticoagulant.

The medicine combination mentioned in this invention was composed by theherbs of the special weight as following:

Chuanxiongiong 10 g-25 g

Tianma 1.5 g-8 g

The better weight proportion of the two herbs is that:

Chuanxiongiong 8 g-15 g

Tianma 2 g-6 g

The best weight proportion of the two herbs is that:

Chuanxiongiong 10 g

Tianma 2.5 g

According to the special compatibility of the herbs mentioned above andby the regular pharmaceutics method, the medicine combination in thisinvention can be made into any of the normal dosage forms, such as thecapsule, the water-soluble powder, the tablet, the pellet, the oralliquid and the drop pills. The optimal form is the capsule. In theproducing process, a regular excipient such as amylo and silicon dioxidecan be added in the medicine combination.

The preparation of the medicine combination of the present invention isthat: in the proportion of the present invention, Chuanxiongiong andTianma of the special weight are dehydrated, smashed and mixed together.The mixed powder is extracted in the cycling 90% alcohol solution. Theextracted liquids are merged and filtrated. Then the extracted solutionis condensed to the clear cream at the relative density of 1.27 and atthe degree ranged from 55° C. to 60° C. The gruffs are cooked in water,and then the extracted water solutions are merged and filtrated. Thesolution is condensed to the clear cream at the relative density of 1.27and at the temperature ranging from 55° C. to 60° C. and then all theclear cream is combined together. The excipient is added into the mixedcream, and then the new cream is dehydrated in the vacuum, smashed andfiltrated. Capsule the medicine powder and obtain the final medicinecapsule.

In the preparation mentioned, the 90% alcohol solution can be used twiceto extract the mixed raw herbs powder, and each time for 2 hours. Thegruffs can be cooked twice, and each time for 1 hour.

The invention medicine has the function of curing the wind syndrome ofhead, the dizziness and blurred vision. It is also good at dispellingthe wind and cold in the Yang channel, dispersing and expelling thephlegm in the chest, and treating the splitting and normal headache. Itcan also relieve the body constriction and listlessness, refresh themind, and open the orifice. It has an obvious effect on thecardiovascular system, the blood system and the central nervous system.The effects on these systems are as follows:

1. The effect on the cardiovascular system: (1) the antianoxic function:The invention medicine can enhance the mouse's tolerance to the anoxicsituation in the normal atmosphere pressure, and prolong the time ofdeath in the oxygen free environment. It can lower the heart'stime-tension index (TTI) of the anesthetic dog, and reduce the cardiacmuscle's oxygen consumption. (2) The function of lowering BP: Not onlycan it lower the BP of the normal rat and dog in the anestheticcondition, but also lowers the BP, renin activity and the aldosteroneconcentration of the renal hypertension rat (Goldblatt rat) and thespontaneous hypertension rat. The fact indicates that the effect oflowering the BP is accomplished by regulating the RAS system.

2. The effect on the blood system: (1) The function of inhibiting theplatelet aggregation: This invention medicine can not only suppress therabbit's and rat's platelet aggregation induced by the ADP, but suppressthe rat's experimental thrombosis. (2) The function of anticoagulation:the medicine can prolong the rat's thrombin time (TT) and the kaolinpartial thrombin time (KPTT), and enhance the anticoagulation activityof the plasma.

3. The effect on the central nervous system: (1) The function oftranquilizing; (2) The function of antalgic: it can relieve the paincaused by the heat, the electricity and the chemical reagent.

Another advantage of this invention medicine lies in that thatChuanxiong has the function of activating blood circulation to dissipateblood stasis and meliorating the blood circulation of the brain, andthat Tianma has the function of relieving the pain caused by contractureand spasm and meliorating the vascular function. When the two herbs areused together, they can create a synergetic effect. Chuanxiong, whichcan activate blood circulation and dissipate blood stasis, makes theblood flow smoothly in the vessel. Additionally, it can promotecirculation of Qi to relieve the pain. It is the king medicine in theinvention medicine combination. Tianma, which has the even nature andthe sweet flavor, can calm the wind and arrest convulsion. It is good atcuring the dizziness, the wind syndrome of head, the headache and thenumbness of the limbs. It is good at going to the upper orifices andmakes up the best compatibility with Chuanxiong to treat vascularheadache. The combination of the two herbs has a good effect to relievethe tendencies of “dense, congregate, stasis”, that is thecharacteristic of the blood-stasis-type patients. The compound has abetter effect than the single herb. Toxicology experiments indicatedthat: the Daxiong (made by the method of the present invention and namedafter Daxiong capsule) capsule's LD₅₀ amounts by single administrationon mouse are as follows: intravenous injection (4.01±0.41 g/kg);intraabdominal injection (14.03±1.12 g/kg); stomach douche (52.19±6.36g/kg). The Daxiong capsule's LD50 amount by single administration on ratby oral administration is 57.36±4.82 g/kg. Rats which have taken theDaxiong capsule continuously on the amount of 7.5, 15.0 g/kg for 3months showed no toxic reaction. This amount is 10-20 times of theclinical dosage.

In addition, the clinical experiment proved that: the Daxiong capsule'stotal effective rate is 89.05%, which is remarkable higher than 72%effective rate of the commonly used similar medicine—“Yuntongding”. Thetotal effective rate in patients with hyperactivity of liver-yang is90.91%, while the rate in the patients of internal accumulation of bloodstasis is 72%. The effective rate is obviously higher than that of the“yuntongding”.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Practice Example 1

Chuanxiongiong 784 g and Tianma 196 g were taken, then the raw herbswere dehydrated, smashed and mixed. The powder was extracted with the90% alcohol solute twice, each time for 2 hours. The extracted solutionwas collected, then filtered and the colature condensed to the clearcream at the relative density of 1.27 (55-60° C.) The gruffs were cookedin the water twice, each time for 1 hour. The extracting solution wascollected and filtered then the solution was condensed to the clearcream at the relative density of 1.27(55-60° C.). The clear cream wasmixed together with the cream mentioned above, then silicon dioxide 49 gwas added to it. The medicine was dehydrated in the vacuum, smashed andthe powder filtrated, then medicine was capsulated into 1000 capsules.

Practice Example 2

The Invention Medicine's Effect on the Cardiovascular System

1. The influence on mice in the situation of anoxic and normalatmosphere pressure: male NIH mice weighing 18-22 g were divided into 7groups at random, and 10 mice to a group. After feeding the mice theDaxiong capsule for 0.5 h, 1.2 h, 3 h and 4 h, the mice were enclosed inconical flasks—each conical flask's volume is 165 ml and each flask has2 g soda lime, which can absorb the CO₂ and the vapor. The results areshown in Table 1. According to the data, the Daxiong capsule can enhancethe mice's endurance to the anoxic situation. Compared with the controlgroup, the mice fed with the Daxiong capsule on the dosage of 7.5 g/kg,15.0 g/kg survived 8.87% (P>0.05), 20.44% (p<0.010) longer than the micein the control group. This effect lasted 3 hours.

TABLE 1 Daxiong capsule's influence to the mice's survival time in thesituation of anoxic at normal atmosphere pressure. Adminis- Adminis-Number Dosage tration tration of Medicine (g/kg) way time mouse Survivaltime Control — PO 0.5 10 20′18″ ± 1′5″ group Daxiong 7.5 PO 0.5 10 22′6″± 1′7″ capsule Daxiong 15.0 PO 0.5 10 24′27″ ± 46″** capsule Daxiong15.0 PO 1 10 24′34″ ± 1′36″* capsule Daxiong 15.0 PO 2 10 24′39″ ±1′37″* capsule Daxiong 15.0 PO 3 10 24′31″ ± 1′10″* capsule Daxiong 15.0PO 4 10 19′47″ ± 1′2″ capsule Note 1): Compared to the control group, *means P < 0.05, ** means P < 0.01, *** means P < 0.001, and thesesymbols will represent the same meaning in the other practice examplesfollowing.

2. The blood-pressure-lowering function

2.1 The acute blood-pressure-lowering function on anaesthetic dogs:Mongrels weighing 13-18 kg, including males and females, were chosen,then the mongrels were anesthetized by injecting the pentobarbitalsodium into the vein on the dosage of 30 mg/kg. The pressure transducerwas connected to the mongrels' common carotid artery, then the SBP andMBP were recorded by the PPF-5 carrier amplifier, at the same timerecording the II lead of the ECG by the RB-5 biophysical amplifier andthe HR by the RT-5 cardiotachometer. By calculating the square root ofSBP and HR's product, the TTI (time tension index) was deduced.Memorizing the indexes in the RM-86 recorder, five minutes after theindexes turning to be stable, the Daxiong capsule solution (all thesolution was the invention medicine dissolved in 20 ml 0.9% NS) wasinjected in the mongrels' femoral vein on the dosage of 62.5 mg/kg,125.0 mg/kg, 250.0 mg/kg. After the injection, HR was obviously reduced,and the peak values of the decreasing amplitude are 4.8% (p<0.01), 34.1%(P<0.05), 48.9% (p<0.001), 32.3% (P<0.01). The influence of Daxiongcapsule on the HR, MBP, TTI can remain about 0.5 h. Additionally, theprocess has a certain dose-effect relationship and a time-effectrelationship. Daxiong capsule has no effect on the ECG. The results areshown in Table 2.

TABLE 2 The Daxiong capsule's influence on the HR, MBR, TTI of theanesthetic dogs num- ber before dosage of adminis- after administrationIndex medicine (mg/kg) dog tration 1′ 5′ 10′ 15′ 30′ HR Control group —6 183.4 ± 4.2 183.4 ± 4.2 184.6 ± 3.8 184.2 ± 3.8 184.2 ± 3.8 183.0 ±3.9 (times/ Daxiong capsule 62.5 6 179.8 ± 10.5 177.6 ± 11.7 170.3 ±10.5* 165.0 ± 10.6*** 169.7 ± 13.3* 179.5 ± 17.8 min) Daxiong capsule125.0 6 168.3 ± 7.3 153.2 ± 9.9* 149.7 ± 10.3* 151.5 ± 7.1*** 151.7 ±8.2*** 157.8 ± 9.4* Daxiong capsule 250.0 6 163.7 ± 13.2 132.5 ± 15.6**135.2 ± 13.9* 138.0 ± 13.9* 141.8 ± 13.3* 152.8 ± 13.4* MBP controlgroup — 6 146.8 ± 4.9 148.8 ± 4.6 148.8 ± 5.8 150.0 ± 5.2 149.6 ± 5.2148.8 ± 4.6 (mmHg) Daxiong capsule 62.5 6 140.7 ± 6.7 134.0 ± 7.8**135.0 ± 7.0** 134.0 ± 7.9*** 134.3 ± 7.2** 135.0 ± 6.2 Daxiong capsule125.0 6 147.3 ± 3.4  97.0 ± 15.8* 115.7 ± 8.4* 123.7 ± 6.3* 127.7 ± 6.2*136.7 ± 4.7* Daxiong capsule 250.0 6 149.3 ± 7.1  76.3 ± 13.5*** 106.7 ±13.1* 117.0 ± 12.1* 124.0 ± 10.6* 138.3 ± 7.8* TTI control group — 6174.3 ± 4.5 176.6 ± 4.0 177.7 ± 4.4 178.1 ± 3.4 177.9 ± 4.6 175.6 ± 4.3Daxiong capsule 62.5 6 166.6 ± 8.0 163.1 ± 8.8 159.6 ± 8.5* 160.3 ±7.9*** 157.8 ± 9.0* 165.1 ± 11.5 Daxiong capsule 125.0 6 167.6 ± 5.1136.4 ± 16.6 145.9 ± 12.1 150.3 ± 8.7* 151.3 ± 9.0* 158.3 ± 7.3* Daxiongcapsule 250.0 6 164.7 ± 8.1 111.5 ± 12.6** 128.4 ± 12.4** 137.0 ± 11.4**142.2 ± 10.7* 154.8 ± 9.2**

2.2 The blood-pressure-lowering function on the Goldblatt rat. Wistarrats weighing 160-200 g were chosen and the rats were anestetized byinjecting sodium pentobarbital into the abdominal cavity on the dosageof 30 mg/kg. The left renal artery was clamped to be narrow by thesilver clip with the inside diameter of 0.20 mm or 0.25 mm, and theright kidney left untouched. Five weeks later, the rats were dividedinto groups equably on the level of BP and BW. The treatment groups wereinjected with Daxiong capsule solution into the stomach once a day for 3weeks on the dosage of 5 g/kg, 10 g/kg, 20 g/kg, while the control groupwas injected with distilled water on the same dosage. Record the BP andHR once a week by the CRS-III BP-HR-meter to observe the change processof HB. The BP of the rats which were fed with Daxiong capsule on thedosage of 20 g/kg for 1 week lowered for 16.25% (P<0.01), compared withthe control group, while it took 3 weeks for the group fed on the dosageof 10 g/kg to lower BP to the same level. The group fed with thepositive compare medicine also had an obvious BP decrease. The resultsare shown in Table 3.

TABLE 3 Daxiong capsule's influence on the BP (mmHg) of the renalhypertension rats dose administra- number before after administrationmedicine (g/kg) tion way of rats administration 1/2 (week) 1 (week) 2(week) 3 (week) (control (same PO 6 189.0 ± 4.8 214.5 ± 9.7 220.9 ± 19.2229.9 ± 7.0 245.4 ± 7.9 group) volume) distilled water Daxiong  5 PO 8191.2 ± 4.0 212.4 ± 9.5 220.8 ± 15.3 215.5 ± 10.2 235.2 ± 9.3 capsuleDaxiong 10 PO 8 190.0 ± 4.4 203.3 ± 7.4 195.3 ± 8.7 204.5 ± 13.5 205.5 ±7.6** capsule Daxiong 20 PO 8 190.5 ± 4.3 188.1 ± 10.9 191.7 ± 10.7**190.1 ± 11.6*** 195.2 ± 15.3* capsule Captopril 2 × 10-2 PO 6 190.8 ±4.9 155.6 ± 5.2** 147.8 ± 7.1** 151.1 ± 12.9** 143.5 ± 11.5**

2.3 The influence to the BP, PRA, AID of the spontaneous hypertensionrat (SHR): 3-month-old SHR weighing about 150 g were divided into groupsaccording to the BP, BW. The administration way, dosage, time and themeasure method were the same as the experiment above. At the same time,3-month-age normal WKY rats were chosen as the control group. 2 hoursafter the final administration, the rats were decapitated and the bloodcollected. The activity of renin and aldosterone were measured by theway of ELISA. The results demonstrated that the BP of the rats fed withthe Daxiong capsule on the dosage of 5 g/kg, 10 g/kg, 20 g/kg for oneweek had a remarkable decrease by 3.35% (p<0.05), 8.02% (p<0.01), 11.19%(p<0.001). The decrease amplitude is on a direct ratio to the dosage andremained at a steady level for three weeks. (Table 4). Additionally, thePRA and AID were on the obviously lower level than the control group.(Table 5)

TABLE 4 Daxiong capsule's influence to the HB of the SHR administrationnumber before after administration medicine dosage (g/kg) way of miceadministration 1/2 (week) 1 (week) 2 (week) 3 (week) normal group samevolume PO 13 112.8 ± 1.5 111.2 ± 1.0 115.1 ± 1.3 111.5 ± 5.3 110.7 ± 1.3distilled water control group same volume PO 13 170.5 ± 2.5 171.5 ± 2.4173.3 ± 1.4 178.5 ± 1.8 180.1 ± 2.1 distilled water Daxiong capsule  5PO 13 170.8 ± 2.4 168.4 ± 2.3 167.5 ± 2.3 170.4 ± 3.0 165.2 ± 3.2Daxiong capsule 10 PO 13 170.6 ± 2.9 160.9 ± 2.5** 159.4 ± 1.6** 159.2 ±2.3 157.3 ± 1.9*** Daxiong capsule 20 PO 13 170.1 ± 2.9 159.2 ± 2.7**153.9 ± 2.8*** 154.3 ± 1.4** 151.8 ± 1.4*** captopril 2 × 10-2 PO 12170.5 ± 2.9 113.5 ± 3.9*** 138.2 ± 3.6*** 142.3 ± 1.8*** 140.0 ± 2.0***

TABLE 5 Daxiong capsule's influence to the PAR, AID of the SHR admin-istra- dosage tion number PRA AID medicine (g/kg) way of mice (ng/ml/h)(ng/ml) normal — — 13 4.66 ± 0.69 — group control — PO 13 9.81 ± 0.982.78 ± 0.10 group Daxiong 1.25 PO 13 4.78 ± 0.77*** 1.94 ± 0.16***capsule Daxiong 2.50 PO 13 2.69 ± 0.67*** 2.29 ± 0.12** capsule

Practice Example 3

This Medicine's Influence to the Blood System

1 The influence on the platelet's aggregative character.

1.1 The influence on the rabbit platelet's aggregative character: Rabbitplatelet plasma was prepared according to the Csalay's method. Lucidrabbit's blood was collected by carotid arterial cannula, then the bloodwas mingled with 3.8% sodium citrate in proportion of 9:1 toanticoagulate. The mixture was centrifuged on the speed of 1000 rpm for5 minutes then at the speed of 3000 rpm for 10 minutes. The blood plasmawas separated into the platelet-rich plasma and the platelet-absentplasma. When conducting the measurement, the platelet aggregationpercent was regulated to 50-60%. The platelet aggregation experiment wasperformed according to the Born's method by the PPP autobalanceplatelet-aggregation-machine (type SPA-3), keeping the concentrate ofADP(the aggregation inducer) at 12 μM, then collecting the data andcomparing the aggregation percents between the treatment group and thecontrol group at the 5^(th) minute. The results are shown in Table 6.Daxiong capsule can remarkably inhibit the rabbit platelet's aggregationcharacter: at the drug concentration 1.95 mg/ml, 3.90 mg/ml, theplatelet aggregation percents were 46.73±1.95% (P<0.01), 37.98±3.00%(P<0.001)

TABLE 6 Daxiong capsule's influence on the rabbit platelet aggregationcharacter. Concentration number of aggregation medicine (mg/ml)experiments percent (%) Control group 9 57.73 ± 2.39 Daxiong capsule1.95 6 46.73 ± 1.59** Daxiong capsule 3.90 6 37.98 ± 8.00*** Aspirin0.27 6 39.94 ± 2.05***

1.2 The influence on the rat platelet aggregation character: Wistar ratsweighing 180-210 g, including males and females, were chosen then fedwith Daxiong capsule by gastric administration. 1.5 hour after theadministration, the blood from the abdominal aorta was collected on thecondition of anesthesia by ether. The platelet plasma was prepared bythe same method mentioned above, and the PLT aggregation experimentperformed by the same machine with a different ADP concentrate of 2.8μM. Comparing the two aggregation percents, we got the results shown inTable 7. As the table shows, eating Daxiong capsule can inhibit the ratPLT aggregation. At the dosage of 5 g/kg, 10 g/kg, the rat's largestplatelet aggregation percents were 37.35±5.06% (P<0.01), 631.14±5.02%(P<0.01).

TABLE 7 Daxiong capsule's influence on the rat platelet aggregationcharacter. dosage administration number platelet aggregation medicine(g/kg) way of rat percent (max) Control PO 6 54.00 ± 4.23 group Daxiong 5 PO 6 37.35 ± 5.06* capsule Daxiong 10 PO 6 31.14 ± 5.02** capsuleAspirin 2.7 × 10-2 PO 6 31.06 ± 3.80**

1.3 The influence on the rat's experimental thrombosis: Male Wistar ratsweighing 270-370 g were chosen to be anaesthetized by belly injection ofsodium pentobarbital on the dosage of 50 mg/kg, then the rats were fixedat the supine position and the right common carotid artery and the leftexternal jugular vein were detached. A polyvinyl pipe of 19.5 cm longwith the inside diameter of 1.5 mm embedded in a 5.0 cm-long type 4suture and filled with the solution of heparin and normal saline (25μ/kg) was inserted into the right common carotid artery one end and theleft external jugular vein the other end. The pipes were opened, thenthe extracorporeal circulations were built up 1 hour after the rats werefed with Daxiong capsule. 15 minutes later, the pipe was closed, thesuture taken out and the greenweight measured. The results are shown inTable 8. Daxiong capsule has a remarkable inhibitory action on thethrombosis. The inhibitory ratios were 15.39% (P<0.25), 24.33% (P<0.01)on the dosage of 5 g/kg, 10 g/kg.

TABLE 8 Daxiong capsule's influence on the rat experimental thrombosisdosage administration number greenweight of medicine (g/kg) way of ratthrombus (mg) Control group — PO 10 25.40 ± 1.10 Daxiong capsule 5 PO 1021.49 ± 1.08* Daxiong capsule 10 PO 10 19.22 ± 1.62** Aspirin 0.05 iv 618.28 ± 1.28*

2. The influence on the TT and KPTT of the rat. Wistar rats weighing250-300 g were chosen and blood sampled from abdominal aorta under theanesthetic condition by ether. The blood was mixed with the 3.8% sodiumcitrate in proportion of 9:1 and centrifuged (3000 rpm×20 min) to getthe no-platelet plasma. The experiments following were done on the PPPautobalance platelet-aggregation machine (type SPA-3):

(1) TT measurement: 0.2 ml of thrombase solution (the control group's TTwas regulated to 6-18 s with the same thrombase solution) was added tothe medicine in the cuvette to be incubated together. 5 minutes later0.1 ml of plasma was added in the cuvette, then the time quantum fromthis point to the time that the solution's optical density suddenlychanged was recorded as the TT.

(2) KPTT measurement: 0.1 ml of kaolin partial thrombase suspendingliquid (the KPTT of the control group was regulated to 36-38 s with thesame suspending liquid) and 0.1 ml plasma were added into the cuvette,which contained with the medicine. The mixture was incubated for 3 min.0.1 ml of 0.03 M NaCl₂ was added in the mixture and the time quantumfrom this point to the time that the suspending liquid's optical densitysuddenly changed was recorded as the KPTT. The experiment results areshown in Table 9.

The TT of the treatment groups prolonged by 18.79% (P<0.01), 30.30%(P<0.001) on the dosages of 1.25 mg/ml, 2.50 mg/ml than the TT of thecontrol group, while the APTT prolonged by 5.35% (P>0.05), 10.16%(p<0.05) compared to the control group. The result indicated thatDaxiong capsule can remarkably prolong the blood clotting time andenhance the activity of the blood anticoagulation.

TABLE 9 Daxiong capsule's influence on the rat TT and KPTT. drugconcentration number of medicine (mg/ml) experiment TT (s) KPTT (s)control — 7 16.5 ± 0.5 37.4 ± 0.6 group Daxiong 1.25 7 19.6 ± 0.6** 39.4± 2.4 capsule Daxiong 2.50 7 21.5 ± 0.6*** 41.2 ± 1.2* capsule

Practice Example 4

The Invention Medicine's Influence on the Central Nervous System

1.1 The influence on the mouse's spontaneous activity. Kunming miceweighing 18-22 g were chosen and divided into groups at random. Eachgroup was made up of 10 mice. The mice were put into thethree-optical-track mouse activity recorder (type GJ-7902) to count theamount of mice's spontaneous activity, 50 minutes after the treatmentgroups' mice were fed with the medicine on the dosage of 2.5 g/kg, 5.0g/kg, 10.0 g/kg and the control group's mice were fed with the samevolume distilled water. The results showed that Daxiong capsule canremarkably decrease the normal mice's spontaneous activity. According tothe different dosages, the inhibition ratios were 31.41% (P<0.05),36.54% (P<0.05), 43.90% (P<0.01).

TABLE 10 Daxiong capsule's influence on the mice's spontaneous activity.Admin- istra- Number Dosage tion of Amount of Medicine (g/kg) way mousespontaneous activity Control group PO 20 378.8 ± 36.9 Daxiong capsule2.5 PO 10 259.8 ± 16.6* Daxiong capsule 5.0 PO 10 240.4 ± 31.9* Daxiongcapsule 10.0  PO 10 212.5 ± 27.5** tetrahydropalmatine 5 × 10-2 PO 10 24.3 ± 4.3***

1.2 The influence on the mouse's sleep time caused by sodiumpentobarbital: Male NIH mice weighing 18-22 g were chosen to be dividedinto 3 groups, 10 mice each group. The mice in treatment group wereinjected with a solution of Daxiong capsule into the abdominal cavity onthe dosage of 1.25 g/kg, 2.5 g/kg, while the mice in the control groupwere injected the same volume of normal saline. Ten minutes later, eachmouse was injected with sodium pentobarbital on the dosage of 35 mg/kg.The time when the righting reflex disappeared was recorded. The resultsproved that Daxiong capsule can synergize the effect of the sodiumpentobarbital and prolong the sleep time caused by the sodiumpentobarbital (Table 11). According to the different dosage, the sleeptimes were prolonged 48.04% (P<0.05), 119.62% (P<0.001), compared to thecontrol group.

TABLE 11 Daxiong capsule's influence on the mice's sleep time. DosageAdministra- Number Medicine (g/kg) tion way of mouse Sleep time Control— ip 10 15′43″ ± 3′44″ group Daxiong 1.25 ip 10 23′16″ ± 3′6″* capsuleDaxiong 2.50 ip 10 34′31″ ± 2′31″*** capsule

2 The Function of Antalgic

2.1 The influence on the mouse's reaction to the heat: The experimentreferred to the mouse hot-plate method: female NIH mice weighing 18-22 gwere put on the type CS501 ultra thermostat's metallic plate, on whichthe temperature was 55.0±0.5° C. The action of sucking the postpedes andjumping were concerned as the indexes to the pain caused by the heat andthe shortest time when the mouse shown the indexes was defined as thepain threshold. The sensitive mice whose pain threshold were shorterthan 30 s were chosen and divided into 4 groups according to their painthreshold, each group including 10 mice. The mice were injected with thesolution of Daxiong capsule into the abdominal cavity on the dosage of2.5 g/kg, 5.0 g/kg, then the pain thresholds were measured at time of0.5 h, 1 h, 3 h and 5 h after the administration. If the threshold wasbeyond 60 s, it would be recorded as 60 s. The results are shown inTable 12. Daxiong capsule can improve the mouse's pain thresholdremarkably, and the effect-dose relationship, time-dose relationshipwere both the direct ratio. The group in which the mice were fed withDaxiong capsule on the dosage of 2.5 g/kg improved the pain threshold by87.68% (p<0.01), and the effect lasted 1 hour. The group on the dosageof 5.0 g/kg improved the pain threshold by 148.74% (p<0.001), and theeffect lasted 5 hours.

TABLE 12 Daxiong capsule's influence on the mouse's pain threshold(hot-plate method) dosage administration number before afteradministration Medicine (g/kg) way of mouse administration 1/2 (h) 1 (h)3 (h) 5 (h) Control — ip 10 20.3 ± 1.2 23.1 ± 2.3 20.0 ± 2.3 20.0 ± 2.218.5 ± 1.8 group Daxiong 2.5 ip 10 20.3 ± 1.2  1.8 ± 2.5* 38.0 ± 3.2**30.6 ± 4.9 29.3 ± 4.8 capsule Daxiong 5.0 ip 10 19.9 ± 0.0 38.7 ± 6.8*42.7 ± 3.8*** 44.1 ± 4.6*** 49.5 ± 3.8*** capsule Morphine 1.5 × 10-2 ip10 22.5 ± 2.4 >60 >60 >60 >60 hydrochloride

2.2 The influence on the rat's reaction to the heat. The experimentreferred to the rat's tail-whipping method: SD white rats weighing180-220 g were chosen and the distal ⅓ of their tails were dipped intohot water in which the temperature was regulated to 55.0±0.5° C. by theCS501 ultra thermostat. The tail's whipping out of the water was definedto be the index of pain. The rats were divided equably into 5 groupsaccording to the pain threshold and each group had 9 rats. The rats inthe 3 groups (exclude the control group and the positive medicine group)were fed with the Daxiong capsule on the dosage of g/kg, 10 g/kg, 20g/kg, then the pain thresholds at 0.5 h, 1 h, 2 h and 4 h were measured.The results proved that Daxiong capsule can improve the rat's painthreshold obviously, the effect's intensity and time had a directrelationship with the dosage (Table 13). On the dosage of 0 g/kg, 20g/kg, Daxiong capsule could improve the pain threshold by 40.63%.(p<0.05), 64.52% (P<0.05), the duration of effect was 1 h, 4 h.

TABLE 13 Daxiong capsule's influence on the rat's pain threshold(tail-whipping method) dosage administration number before afteradministration medicine (g/kg) way of rat administration 1/2 (h) 1 (h) 2(h) 4 (h) Control — PO 9 3.1 ± 0.3 0.2 ± 0.5 3.6 ± 0.3 2.6 ± 0.2 2.5 ±0.3 group Daxiong 2.5 PO 9 3.2 ± 0.5 3.8 ± 0.5 3.4 ± 0.3 3.2 ± 0.3 2.7 ±0.2 Capsule Daxiong 5.0 PO 9 3.2 ± 0.3 4.1 ± 0.4 4.5 ± 0.4* 3.2 ± 0.32.6 ± 0.1 Capsule Daxiong 20   PO 9 3.1 ± 0.4 4.2 ± 0.3* 5.1 ± 0.6* 4.7± 0.6* 4.9 ± 0.4* capsule Morphine 1.5 × 10-2 PO 9 3.2 ± 0.3 9.2 ±0.8*** 5.7 ± 0.4** 4.5 ± 0.4* 3.3 ± 0.4 hydrochloride

2.3 The influence on the electrostimulation of mouse: The experimentmethod adopted was to simulate the mouse's vola with the electricity.Female NIH mice weighing 18-22 g were chosen and put on the conductivecopper-wire plate of the YSD-4 multipurpose apparatus's zoopery box. Theelectricity was switched on and the time when the mouse shrieks waschosen as the index of pain threshold. The sensitive mice whose painthresholds were shorter than 15 s were chosen to do the experiment. Themice were fed with Daxiong capsule on the dosages of 5 g/kg, 10 g/kg,then the pain thresholds were recorded 60 minutes after theadministration. If the pain threshold was longer than 45 s, the painthreshold would be recorded as 45 s. The results proved that Daxiongcapsule could improve the mice's pain thresholds remarkably in theelectrostimulation experiment. On the dosages of 5 g/kg, 10 g/kg, thepain thresholds were improved by 68.42% (p<0.05), 166.67% (p<0.01).

TABLE 14 Daxiong capsule's influence on the mouse's pain threshold inthe electrostimulation experiment before after dosage administra- numberadminis- adminis- Medicine (g/kg) tion way of mouse tration trationControl — PO 14 3.2 ± 0.3 3.5 ± 0.7 group Daxiong 5 PO 14 3.8 ± 0.5 6.4± 0.4* capsule Daxiong 10 PO 14 3.6 ± 0.5 9.6 ± 2.3** capsule amino-0.05 ip 14 4.8 ± 1.0 21.3 ± 5.5* pyrine

2.4 The influence on the chemical stimulation of the mouse: Theexperiment method was the mouse's body-twisting method. Female NIH miceweighing 18-22 g were divided into groups at random and each group had10 mice. The mice were fed with the solution of Daxiong capsule on thedosages of 1.25 g/kg, 2.50 g/kg, 5.00 g/kg. 60 minutes later all themice were injected 0.8% ethanoic acid into the abdominal cavity on thedosage of 0.1 ml/10 g. The number of the mice's body twisting in thefollowing 20 minutes were recorded as the index. The results indicatedthat Daxiong capsule could reduce this index obviously. The inhibitionpercents were 27.37% (p<0.01), 54.32% (p<0.001), 76.75% (p<0.001) on thedosages of 1.25 g/kg, 2.50 g/kg, 5.00 g/kg.

TABLE 15 Daxiong capsule's influence on the mouse's body-twistingreaction. dosage administration number Medicine (g/kg) way of mousetwist times Control group — PO 10 48.6 ± 2.19 Daxiong capsule 1.25 PO 1035.3 ± 2.94** Daxiong capsule 2.50 PO 10 22.2 ± 1.93*** Daxiong capsule5.00 PO 10 11.3 ± 1.94*** aminopyrine 0.10 ip 10  2.8 ± 1.3***

Practice Example 5

The clinical Test of the Medicine of the Invention

1 General Data

1.1 Case source: All cases were patients treated from January 1993 toJuly 1993, including 281 in hospital and 157 outpatient, for a total of438 patients. Among them, Longhua hospital of Shanghai university ofT.C.M provided 105 patients, Shuguang hospital of Shanghai university ofT.C.M. provided 44 patients, Yueyan hospital of Shanghai university ofT.C.M. provided 60 patients, Ruijin hospital of Shanghai No.2 medicaluniversity provided 89 patients, the attached hospital of Tianjinmedical academy provided 40 patients, the No.2 attached hospital ofTianjin T.C.M. academy provided 40 patients, the No.1 attached hospitalof Tianjin T.C.M. academy provided 60 patients (Refer to Table 16). Allcases were selected according to choice criterion.

TABLE 16 Case and grouping therapy control opening group group grouptotal Shanghai Yueyang hospital 60 60 Shanghai Shuguang hospital 44 44Shanghai Longhua hospital 36 35 34 105 Shanghai Ruijin hospital 35 35 1989 The attached hospital of Tianjin 40 40 medical academy The No. 2attached hospital of 40 40 Tianjin T.C.M The No. 1 attached hospital of30 30 60 Tianjin T.C.M Total 101 100 237 438

1.2 Case Selection

1.2.1 According to diagnose criterion of traditional Chinese medicine asfollows:

1.2.1.1 The Diagnose Criterion of Excessive Rise of Liver-yang Syndrome

Main syndrome: (1) headache and dizzy (2) tongue proper is red andtongue fur is light yellow (3) stringy and slippery pulse

Secondary syndrome: (1) vexation and irritability (2) insomnia (3)hypochondriac pain and bitter taste in the mouth (4) gloomy mood

Diagnosis: the patients possess main syndrome and two of the secondarysyndrome (or more than two) can be diagnosed as excessive rise ofliver-yang syndrome.

1.2.1.2 The Diagnosis Criterion of Internal Stagnation of the BloodSyndrome

Main syndrome: (1) chronical headache (2) tongue proper is dark purpleor have petechia (3) Xi and Se pulse

Secondary syndrome: (1) headache like prick (2) the locate of headacheis changeless (3) feel sick and vomiting

Diagnosis: The patients possess main syndrome and two of the secondarysyndrome (or more than two) can be diagnosed as internal stagnation ofthe blood syndrome.

1.2.2 According to diagnose criterion of western medicine as follows:

Paroxysmal headache, most was pulsation, with the symptom of autonomicnerve dysfunction such as sickness and vomiting, headache paroxysm haveintermittence, there can be sight premonitory before headache paroxysm,most with positive family history.

3. Therapy Method

3.1 Drugs

The Daxiong capsule and Yuntongding tablet provided by Tianjin medicineacademe (Made by No.2 pharmaceutical factory of Zhoukou district ofHenan, approve No.: (86) the medicine approved by ministry of healthwith the number Z-11)

3.2 Method

There are altogether 438 cases in the group, among them, we chose 201cases as random double-blinded experiment, other 237 cases as non-randomtherapy. The random double-blinded group used Daxiong capsule andYuntongding tablet, non-random group used Daxiong capsule. The dosage isall 4# Tid, the course of treatment is two months.

3.3 Observation standard:

The times and degree of headache paroxysm; the changes of traditionalChinese medicine syndrome; the laboratory examination before and aftertherapy; rheoencephalogram (REG), Doppler colorful ultrasound (TCD),plasma 5-serotonin (5-HT), plasma thromboxane (TXB₂), plasmaprostacyclin (PGFla), blood rheology, platelets aggregation. Blood Rt,urine Rt, the examination of liver and kidney function; untowardreaction, toxin and side effect of the medicine.

4. Therapy Result

According to the Guide Principle of Clinical Research with New Medicine(Chinese Medicine)

4.1 General curative effect: The 438 cases of this group randomlygrouping, double-blinded compare the therapy result, the group usingDaxiong capsule is 101 cases, apparent 32 cases, efficacy 57 cases,inefficacy 12 cases, effective rate is 88.11%; control group 100 cases,apparent 11 cases, efficacy 61 cases, inefficacy 25 cases, effectiverate is 72%; opening group 237 cases, apparent 70 cases, efficacy 142cases, inefficacy 25 cases, effective rate is 89.45%. The averageeffective rate of Daxiong capsule is 89.05%, apparent rate is 0.18%.Details are shown in Table 17

TABLE 17 Curative effect analysis apparent efficacy inefficacy Generalnum- num- num- effective total ber % ber % ber % rate Treat 101 32 31.6857 56.43 12 11.88 88.11 group control 100 11 11.00 61 61.00 28 28.0072.00 group opening 237 70 29.53 142  29.91 25 10.54 89.45 group

The Radit Analysis Between Control Group and Treat Group u=3.5901 (u isthe Figure of Statistic Checking, the Follow is Sameness)

4.2 Syndrome curative effect: The 438 cases of this group includeexcessive rise of liver-yang syndrome 246 cases, internal stagnation ofthe blood syndrome 192 cases. The general effective rate of Daxiongcapsule to treat excessive rise of liver-yang syndrome is 90.91%, tointernal stagnation of the blood syndrome is 86.75%. (Table 18)

TABLE 18 Syndrome curative effect analysis Treat group control groupopening group effective effective effective apparent efficacy inefficacyrate apparent efficacy inefficacy rate apparent efficacy inefficacy rateexcessive 17 30 4 92.15 8 33 18 69.49 42 81 13 90.4 rise of liver-yanginternal 15 27 8 84.00 3 28 10 75.60 27 61 12 88.0 stagnation of theblood

The radit analysis between control group and treat group before andafter therapy:

excessive rise of liver-yang: u=3.0202, p<0.01;

internal stagnation of the blood: u=2.0502, p<0.05.

4.3 The reduction of headache paroxysm times before and after therapy:According to the observation, Daxiong capsule can obviously reduce andrelieve headache paroxysm times, Daxiong capsule can obviously reducethe headache paroxysm times. In contrast to the control group, there wasvery remarkable difference (p<0.001), the excessive rise of liver-yangsyndrome group and internal stagnation of the blood syndrome group alsohave very remarkable difference (p<0.001) to control group. (Detailsshown in Tables 19-1, 19-2, 19-3).

TABLE 19-1 Headache paroxysm times before and after therapy (Everymonth) normal 1 time 2 time 3 time and more Case Before After BeforeAfter Before After Before After number therapy therapy therapy therapytherapy therapy therapy therapy Treat 101 0 56 2 36 35 4 64 5 groupcontrol 100 0 22 8 48 37 23 55 7 group opening 237 0 50 10 145 63 23 16419 group total 438 0 128 20 229 135 50 283 31

The radit analysis between control group and treat group after therapy:u=4.7887, p<0.001;

The radit analysis of treat group before and after therapy: u=11.2008,p<0.001.

TABLE 19-2 The excessive rise of liver-yang syndrome headache paroxysmtimes before and after therapy (Every month) normal 1 time 2 time 3 timeand more Before After Before After Before After Before After therapytherapy therapy therapy therapy therapy therapy therapy Treat 51 0 31 217 17 2 32 1 group control 59 0 16 6 29 15 12 38 2 group opening 136 037 8 76 33 14 95 9 group

The radit analysis between control group and treat group after therapy:u=3.4804, p<0.001

The radit analysis of treat group before and after therapy: u=8.2566,p<0.001

TABLE 19-3 The internal stagnation of the blood syndrome headacheparoxysm times before and after therapy (Every month) normal 11 time 21time 3 time and more Number Before After Before After Before AfterBefore After of case therapy therapy therapy therapy therapy therapytherapy therapy Treat 50 0 25 0 19 18 2 32 1 group control 41 0 6 2 1922 11 17 5 group opening 101 0 13 2 69 30 9 69 10 group

The radit analysis between control group and treat group after therapy;u=3.5333, p<0.001

The radit analysis of treat group before and after therapy: u=7.5933,p<0.001

4.4 The improvement of headache paroxysm degree before and aftertherapy:

According to the observation of 438 cases of vascular headache patients,with regard to the improvement of headache paroxysm degree before andafter therapy, there was very remarkable difference (p<0.001) betweencontrol group and treat group. The excessive rise of liver-yang syndromegroup and internal stagnation of the blood syndrome group also showed avery remarkable difference (p<0.001) to control group. (Details areshown in Tables 19-1, 19-2, 19-3)

TABLE 20-1 the improvement of headache paroxysm degree before and aftertherapy normal Light medium serious Case Before After Before AfterBefore After Before After number therapy therapy therapy therapy therapytherapy therapy therapy Treat 101 0 55 34 56 10 45 2 group control 100 017 34 59 45 41 4 group opening 237 0 49 5 142 97 35 135 11 group total438 0 121 5 210 212 90 221 17

The radit analysis between control group and treat group after therapy:u=6.0677, p<0.001

The radit analysis of treat group before and after therapy: u=11.2594,p<0.001

TABLE 20-2 The improvement of the excessive rise of liver-yang syndromeheadache paroxysm degree before and after therapy normal Light mediumserious Case Before After Before After Before After Before After numbertherapy therapy therapy therapy therapy therapy therapy therapy Treat 510 32 15 30 3 21 1 group control 59 0 10 20 31 26 28 3 group opening 1360 34 3 76 58 21 75 5 group

The radit analysis between control group and treat group after therapy:u=5.1654, p<0.001

The radit analysis of treat group before and after therapy: u=8.1727,p<0.001

TABLE 20-3 the improvement of the internal stagnation of the bloodsyndrome headache paroxysm degree before and after therapy normal Lightmedium serious Case Before After Before After Before After Before Afternumber therapy therapy therapy therapy therapy therapy therapy therapyTreat 50 0 23 19 26 7 24 1 group control 41 0 7 14 28 19 13 1 groupopening 101 0 15 2 66 39 14 60 6 group

The radit analysis between control group and treat group after therapy:u=3.4051, p<0.001

The radit analysis of treat group before and after therapy: u=7.7665,p<0.001

5. Clinical Examination Standard Analysis

5.1 The Changes of Plasma 5-serotonin (5-HT ) Before and After Therapy

We observed 349 cases of all 438 cases for changes of plasma 5-serotonin(because one of the hospitals chose not have this examination). Wedivided the 349 cases into high-value group and low-value groupaccording to the examination result before therapy, and observed theimprovement after therapy. The statistics showed the improvement oftreat group is very remarkable (p<0.001) before and with therapy inlow-value group, there was very remarkable difference (p<0.05) betweencontrol group and treat group, but because we did not get enough dataabout syndrome divide group to explain the general effect rate, we didnot divide into two syndrome groups as before, the same as follow data.

TABLE 21 The changes of 5-serotonin (5-HT) before and after therapyanalysis Case number Before therapy After therapy Treat group 66 109.68± 125.57 105.19 ± 92.77  control group 65 124.94 ± 159.18  96.69 ±107.93 opening group 218 100.74 ± 121.64 58.23 ± 37.40

The comparison between control group and treat group: t=0.48 (t is thefigure of statistic checking, the follow is sameness) p<0.05.

TABLE 22 The changes of 5-serotonin (5-HT) analysis according to groupslow-value group (<46) high-value group (>46) Case Before After CaseBefore After number therapy therapy number therapy therapy Treat 2032.30 ± 56.73 ± 16 143.32 ± 126.26 ± group 9.00 25.86 137.57 103.20control 17 32.16 ± 36.22 ± 48 157.79 ± 117.40 ± group 7.65 16.89 173.98118.70 opening 43 29.09 ± 52.78 ± 175 118.35 ± 59.56 ± group 9.30 27.67129.82 39.38

low-value group:

The comparison between control group and treat group after therapy:t=2.52, p<0.05

The comparison of treat group before and after therapy: t=3.71, p<0.001

high-value group:

The comparison between control group and treat group after therapy:t=0.39, p>0.05

The comparison of treat group before and after therapy: t=0.88, p<0.05

5.2 The Changes of Plasma Thromboxane (TXB₂) Before and After Therapy

We observed 428 cases of all 438 cases the changes of plasma thromboxane(TXB₂) before and after therapy. Statistics showed there is a veryremarkable difference before and after therapy (p<0.001). We divided the428 cases into high-value group and low-value group according to theexamination result before therapy, and observed the improvement aftertherapy. Statistics showed that the improvement of treat group is veryremarkable (p<0.001) before and after the therapy in high-value group.Tables 23 and 24 show the results.

TABLE 23 The changes of thromboxane (TXB₂) before and after therapyanalysis Case number Before therapy After therapy Treat group 98 200.15± 110.29 149.53 ± 51.41 control group 94 189.96 ± 102.39 163.63 ± 91.73opening group 236 176.66 ± 105.32 131.72 ± 55.21

The comparison between control group and treat group after therapy:t=1.32, p>0.05;

The comparison of treat group before and after therapy: t=4.78, p>0.001.

TABLE 24 The changes of thromboxane (TXB₂) analysis according to groupshigh-value group (>136) low-value group (<136) Case Case Before Afternum- Before After number therapy therapy ber therapy therapy Treat 22100.92 ± 115.86 ± 76 228.87 ± 159.28 ± group 25.00 44.13 108.78 49.43control 17 102.47 ± 133.83 ± 77 209.28 ± 170.20 ± group 21.77 21.23103.14 97.48 opening 72  69.50 ± 113.05 ± 164 223.71 ± 139.98 ± group41.76 49.25  89.06 55.83

low-value group:

The comparison between control group and treat group after therapy:t=1.15, p<0.05;

The comparison between control group and treat group after therapy:t=1.15, p<0.05;

high-value group:

The comparison between control group and treat-group after therapy:t=0.88, p>0.05;

The comparison of treat group before and after therapy : t=5.56,p<0.001.

5.3 The Changes of Plasma Prostacyclin (PGFla) Before and After Therapy

We observed 428 cases of all 438 cases the changes of plasmaprostacyclin (PGFla) before and after therapy. We divided the 428 casesinto high-value group and low-value group according to the examinationresult before therapy. There is no difference (p>0.05) between the twogroups. Observing the improvement after therapy, statistics showed theimprovement of treat group is very remarkable (p<0.001) before andtherapy in high-value and low-value group. Tables 25 and 26 show theresults.

TABLE 25 The changes of PGFla before and after therapy analysis Casenumber Before therapy After therapy Treat group 98 28.91 ± 18.02 29.56 ±13.56 control group 94 29.84 ± 15.02 29.57 ± 15.64 opening group 23629.57 ± 16.55 24.54 ± 10.36

The comparison between control group and treat group after therapy:t=0.01, p>0.05;

The comparison of treat group before and after therapy: t=0.32, p>0.05

TABLE 26 The changes of PGFla analysis according to groups low-valuegroup (<23.9) high-value group (>23.9) Case Before After Case BeforeAfter number therapy therapy number therapy therapy Treat 44 14.66 ±26.46 ± 54 40.51 ± 32.09 ± group 4.49 6.75  16.50 16.88 control 22 16.68± 26.40 ± 72 33.86 ± 30.55 ± group 6.19 18.66 14.63 14.60 opening 9814.08 ± 22.13 ± 138 40.58 ± 26.25 ± group 5.62 10.15 18.40 10.20

low-value group:

The comparison between control group and treat group after therapy:t=0.54, p<0.05

The comparison of treat group before and after therapy t=11.95, p<0.001;

high-value group:

The comparison between control group and treat group after therapy:t=0.88, p>0.05;

The comparison of treat group before and after therapy: t=2.75, p<0.01;

5.4 The Analysis of Blood Rheology Changes, Before and After Therapy

Because two of the hospitals did not have the blood rheologyexamination, we only observed 206 cases of all the 438 cases. Before andafter therapy, we found that all cases we observed have different degreedescent with packed cell volume, whole blood viscosity, whole blooddeacidizing viscosity and plasma viscosity after therapy, but thestatistics show no difference (p>0.05). Details are shown in Table 27.

TABLE 27 The changes of blood rheology before and after therapy analysis(X ± SD) whole blood Case packed cell whole blood deacidizing plasmanumber volume viscosity viscosity viscosity Treat Before 58 44.98 ± 3.826.88 ± 1.48 10.57 ± 11.14 3.57 ± 9.25 group therapy After 59 59.40 ±3.21 6.25 ± 1.12 7.91 ± 0.80 1.67 ± 0.15 therapy control Before 57 43.53± 4.17 6.70 ± 1.38 8.86 ± 1.37 1.81 ± 0.14 group therapy After 59 41.73± 4.18 6.24 ± 1.16 11.14 ± 15.56 1.71 ± 0.17 therapy opening Before 14244.58 ± 7.61 7.01 ± 5.83 11.51 ± 3.38  1.91 ± 1.36 group therapy After141 41.05 ± 9.65 5.96 ± 5.83 9.58 ± 3.31 1.90 ± 2.55 therapy

The comparison between control group and treat group after therapy:

packed cell volume: t=1.09, P>0.05

whole blood viscosity: t=0.05, P>0.05

whole blood deacidizing viscosity: t=1.60, P>0.05

plasma viscosity: t=1.40, P>0.05

5.5 The Analysis of the Platelets Aggregation's Changes, Before andAfter Therapy

Because three of the hospitals did not have the platelets aggregationexamination, we only observed 142 cases of all the 438 cases. Before andafter therapy, we found that all cases in three groups have differentdegree descent with platelets aggregation, but statistics show nodifference. Details are shown in Table 28.

TABLE 28 The changes of platelets aggregation before and after therapyanalysis Case number Before therapy After therapy Treat group 30 59.20 ±13.11 49.92 ± 7.60  control group 30 57.18 ± 17.35 51.79 ± 12.35 openinggroup 82 67.67 ± 20.65 49.21 ± 17.05

The comparison between control group and treat group after therapy:t=0.7 1, P>0.05

5.6 The Analysis of the Doppler Colorful Ultrasound's (TCD) Changes,Before and After Therapy

In all 438 cases, some hospitals do Doppler colorful ultrasound (TCD) onpatients. We observed in 259 cases the changes before and after therapywith TCD, include treat group 65 cases, control group 65 cases, openinggroup 129 cases, and found that the improvement of treat group is veryremarkable (p<0.001) before and after therapy. There is also aremarkable difference between treat group and control group (P<0.01).Details are shown in Table 29.

TABLE 29 The improvement of TCD before and after therapy Case Beforetherapy After therapy Effective number serious medium light normalserious medium light normal rate (%) Treat 65 2 27 31 5 2 14 16 33 87.7group control 65 2 29 27 7 2 23 29 11 85.1 group opening 129 5 50 36 355 31 32 16 86.9 group

The comparison between control group and treat group after therapy:u=3.1518, P<0.01

The comparison of treat group before and after therapy: u=4.1195,P<0.001

5.7 The Analysis of the Rheoencephalogram's (REG) Changes, Before andAfter Therapy

In all 438 cases, we observed 184 cases the changes before and aftertherapy with REG, including treat group 30 cases, opening group 154cases. We found that the improvement of treat group is very remarkable(p<0.001) before and after therapy. Details are shown in Table 30.

TABLE 30 The improvement of REG before and after therapy case Beforetherapy After therapy effective Group name number hyperkinesia low-flatnormal hyperkinesia low-flat normal rate (%) Treat group 30 2 24 4 14 1687.0% opening 154 12 128 15 3 77 74 88.4% group

The comparison of treat group before and after therapy: u=2.8926, P<0.01

6. Conclusion

The clinical experiment proved that Daxiong capsule have obviousimprovement with Chinese medicine syndrome, clinical symptom, laboratorystandard, etc. The average effective rate of Daxiong capsule is 89.05%,while Yuntongding is 72%. Daxiong capsule is obviously higher thanYuntongding, the statistics showed there is remarkable different betweenthe two groups (P<0.001), proved that Daxiong capsules have theefficiency of promoting blood flow and the circulation of Qi, calmingthe liver and harmonizing the link, dispelling pathogenic wind andalleviating pain. It has good effectiveness to the patient withexcessive rise of liver-yang and internal stagnation of the bloodsyndrome. We proved that Daxiong capsule is a good medicine to vascularheadache with excessive rise of liver-yang (the effective rate is90.91%) and internal stagnation of the blood syndrome (the effectiverate is 86.75%).

Industrial Application

The medicine combination of this invention about headache treatment canavoid blood coagulation to the blood system, can lower theblood-pressure and myocardium oxygen-consumption to cardiovascularsystem, can calm and alleviate pain to nervous system. The clinicaltrial proved that the effective rate of this medicine to treat vascularheadache with excessive rise of liver-yang is 90.91%, to internalstagnation of the blood syndrome is 86.75%. The invention's medicineprescription is convenient. It can be made into a variety of dosageforms such as the capsule, water-solvable-powder, tablet, oral liquid,pill, drop pills, etc by the normal preparation. It has good industrialapplication.

1. A method for preparing a pharmaceutical composition made of herbsbased on the following weight proportion: rhizome of chuanxiong 10 g-25g, and rhizome of tall gastrodia 1.5 g-8 g; the method comprising: (1)dehydrating, smashing, and mixing together rhizome of chuanxiong andrhizome of tall gastrodia to obtain a mixed powder of rhizome ofchuanxiong and rhizome of tall gastrodia; (2) reflux extracting themixed powder of rhizome of chuanxiong and rhizome of tall gastrodia with90% alcohol solution at least once to extract at least one refluxextracted solution; (3) if the mixed powder of rhizome of chuanxiong andrhizome of tall gastrodia is reflux extracted more than once, then thereflux extracted solutions are merged into one reflux extractedsolution; (4) filtering the reflux extracted solution to obtain a refluxfiltrate; (5) condensing the reflux filtrate to a clear cream at arelative density of 1.27 and at a temperature ranging from 55° C. to 60°C.; (6) cooking the gruffs remaining from the alcohol extraction of step(2) of rhizome of chuanxiong and rhizome of tall gastrodia with water atleast once to obtain at least one cooked extracted solution; (7) if thegruffs of rhizome of chuanxiong and rhizome of tall gastrodia arc cookedmore than once, then the cooked extracted solutions are merged into onecooked extracted solution; (8) filtering the cooked extracted solutionto obtain a cooked filtrate; (9) condensing the cooked filtrate to clearcream at a relative density of 1.27 and at a temperature ranging from55° C. to 60° C.; (10) combining the clear creams from steps (5) and (9)together; (11) adding excipient to the combined clear cream; and (12)vacuum dehydrating; smashing; and filtering the cream.
 2. The method forpreparing a pharmaceutical composition of claim 1, wherein the amount ofthe rhizome of chuanxiong is 8 g-15 g and wherein the amount of rhizomeof tall gastrodia is 2 g-6 g.
 3. The method for preparing apharmaceutical composition of claim 1, wherein the amount of the rhizomeof chuanxiong is 10 g and wherein the rhizome of tall gastrodia is 2.5g.
 4. The method of claim 1, wherein the 90% alcohol solution is usedtwice to extract mixed raw herbs powder and wherein the gruffs arecooked twice.
 5. A method of claim 4, wherein the 90% alcohol solutionis used twice to extract mixed raw herbs powder, each time for 2 hours,and wherein the gruffs are cooked twice, each time for 1 hour.
 6. Themethod of claim 1, wherein the preparation is in the form of a capsule,a water-solvable-powder, a tablet, an oral liquid, a pill, or a droppill.
 7. A method for treating vascular headache using a pharmaceuticalcomposition prepared in accordance with any one of claims 1-3,comprising administering the pharmaceutical composition to a patient inneed thereof.
 8. A method for treating neural headache using apharmaceutical composition prepared in accordance with any one of claims1-3, comprising administering the pharmaceutical composition to apatient in need thereof.
 9. A method for treating anoxia using apharmaceutical composition prepared in accordance with any one of claims1-3, comprising administering the pharmaceutical composition to apatient in need thereof.
 10. A method for treating hypertension using apharmaceutical composition prepared in accordance with any one of claims1—3, comprising administering the pharmaceutical composition to apatient in need thereof.
 11. A method for inhibiting plateletaggregation using a pharmaceutical composition prepared in accordancewith any one of claims 1-3, comprising administering the pharmaceuticalcomposition to a patient in need thereof.
 12. A method for inhibitingthe development of thrombosis using a pharmaceutical compositionprepared in accordance with any one of claims 1-3, comprisingadministering the pharmaceutical composition to a patient in needthereof.
 13. A method for inhibiting blood coagulation using apharmaceutical composition prepared in accordance with any one of claims1-3, comprising administering the pharmaceutical composition to apatient in need thereof.